With the recent 'completion' of the human genome sequence, geneticists (including the applicant) have turned their attention to a detailed consideration of variation, both as it occurs in the genome and as it relates to the etiology of common complex traits. The main objective of the research training proposed here is to place the uses and understandings of human variation in a multidisciplinary perspective, both to identify the processes by which scientific understanding is negotiated and constructed, and to consider the ways in which scientific choices determine ethical outcomes. Specifically, the proposed research will 1) identify the historical antecedents of current ideas regarding the genetic basis of complex disease, in particular the Common Disease/Common Variant hypothesis, 2) explore the ways in which 'knowledge' about the genetic basis of complex disease is currently constructed, aiming to identify the forces (scientific, commercial, and political) that have led to the success of the CD/CV model, and 3) use this historical and sociological analysis to inform a detailed look at the ethical and epistemological implications of the current research consensus. To the extent that non-scientific forces and vested interests direct the development of a dominant research paradigm like the CD/CV, epistemological issues may be overlooked or downplayed, with potentially important ethical consequences. Research methods will include extensive archival research (of both primary data reports and related press coverage) as well as semi-structured interviews with human geneticists.